Wang et al. Cell Biosci (2020) 10:147 https://doi.org/10.1186/s13578-020-00512-1 Cell & Bioscience REVIEW Open Access Explore a novel function of human condensins in cellular senescence Hongzhen Wang1,2* , Xin Liu1 and Guiying Li2 Abstract There are two kinds of condensins in human cells, known as condensin I and condensin II. The canonical roles of condensins are participated in chromosome dynamics, including chromosome condensation and segregation during cell division. Recently, a novel function of human condensins has been found with increasing evidences that they play important roles in cellular senescence. This paper reviewed the research progress of human condensins involved in diferent types of cellular senescence, mainly oncogene-induced senescence (OIS) and replicative senescence (RS). The future perspectives of human condensins involved in cellular senescence are also discussed. Keywords: Human condensins, Cellular senescence, Oncogene-induced senescence, Replicative senescence Introduction Although both human condensins have similar com- Condensins were frstly identifed for their fundamen- ponents and alphabetic structure, they show diferent tal roles in establishment and maintenance of mitotic nuclear distribution, localization on chromosomes and chromosome condensation in cell-free system from play distinct roles in chromosome dynamics during mito- Xenopus laevis eggs [1, 2]. Until now, most multicellu- sis [9–13]. lar eukaryotes reported have two kinds of condensins, In detail, during interphase condensin I is present in termed as condensin I and condensin II [3–6]. Te two the cytoplasm, whereas condensin II is enriched within kinds of condensins are also exist in human cells [7–10]. the nucleus [10, 14, 15]. During mitosis, initially conden- Both human condensins are pentameric complexes com- sin II participates in chromosome condensation within posed of shared core SMC2/SMC4 (structural mainte- the nucleus in early prophase, whereas condensin I can nance of chromosomes, SMC) heterodimer(also known interact with chromosomes only after the nuclear enve- as hCAP-E/hCAP-C)and three accessory non-SMC lope breaks down [11]. Human condensin I shows a subunits, including a kleisin subunit and two HEAT- two-step dynamic binding. Once nuclear envelope break- repeat proteins. Tey are hCAP-H(NCAPH), hCAP- down, human condensin I rapidly associated with mitotic D2(NCAP-D2) and hCAP-G(NCAPG) for condensin chromosomes then remained constant from prometa- I and hCAP-H2(NCAP-H2), hCAP-D3(NCAPD3) and phase to late metaphase and chromatin bound human hCAP-G2(NCAP-G2) for condensin II [10–12]. condensin I increased again just from anaphase onset Te canonical roles of human condensins are partici- until late anaphase when it dissociated from chromo- pated in chromosome dynamics, including chromosome somes[11, 12]. Similarly, human condensin I complexes condensation and segregation during mitosis [7–12]. dynamically bind to chromosomes in two steps during prometaphase and early anaphase whereas human con- densin II complexes are stably bound to chromosomes *Correspondence: [email protected] throughout mitosis. Localization of human condensin II 2 Key Laboratory for Molecular Enzymology and Engineering is centrally confned, but condensin I reaches 50% of of the Ministry of Education, School of Life Sciences, Jilin University, ∼ 130012 Changchun, People’s Republic of China the chromatid diameter from its center [16]. It is indi- Full list of author information is available at the end of the article cated that human condensin II but not condensin I is © The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creat iveco mmons .org/licen ses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creat iveco mmons .org/publi cdoma in/ zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Wang et al. Cell Biosci (2020) 10:147 Page 2 of 7 more indispensible for the salt-dependent, reversible condensed state of the nucleus, homologous recombina- reorganization of condensin II-based axes in chromo- tion repair and gene expression during interphase [20, some shaping [17]. Moreover, human condensins show 24–35]. Beyond the multiple roles of human condensins a discontinuous pattern along mitotic chromosomes mentioned above, increasing evidences show a novel and play a major role in controlling the elastic stifness function of human condensins in cellular senescence [36, of metaphase chromosomes. Depletion of condensin II 37]. impacts chromosome mechanics more than depletion Cellular senescence plays important protective roles in of condensin I and stifness of the metaphase chromo- development, tissue homeostasis, wound healing, mul- some is more dependent on condensin II than on con- tiple age-related diseases and cancer [38, 39]. Cellular densin I [18].Tis idea is somewhat inconsistent with a senescence is a stable state of irreversible cell cycle arrest former study. It has been demonstrated that human con- caused by various forms of cellular stresses. Senescent densin I but not condensin II can associate with KIF4A cells lose DNA replication ability and still maintain cel- to confer rigidity to centromeres [19]. During anaphase, lular metabolic activity [40, 41]. Especially, cellular senes- when human condensins are depleted, chromosomes are cence can also be induced by pathophysiological stimuli, formed with improperly structured kinetochores and such as ROS (reactive oxygen species), oncogene acti- chromosome bridges appear in the cell [20]. Likewise, vation, cytotoxic drugs and aging [38]. Nowadays four when human condensins are knocked down or dysfunc- kinds of cellular senescence are recognized, i.e., onco- tion in human cells, chromatin bridges between daugh- gene-induced senescence (OIS), replicative senescence ter cells in anaphase and multiple nuclei in single cells are (RS), stress-induced premature senescence (SIPS) and observed[21, 22]. During telophase, human condensins therapy-induced senescence (TIS) [37, 38, 41, 42]. OIS are involved in the mitotic chromosome conformation is induced by oncogene expression and RS is induced by transformation into the interphase state as well. Recently, telomere shortening [37, 38, 41, 43–45]. SIPS is induced it is identifed telophase as a critical transition between by various external signals, such as UV, hyperoxia, hydro- condensin- and cohesin-driven chromosome folding gen peroxide, etc. [41, 45]. TIS is caused by traditional [23]. Consistently, human condensin II can initiate sis- cancer therapy and it can be an efective way to treat can- ter chromatid resolution during S phase [24]. Altogether, cer while lessening side efects [42, 46–48]. the diferences in the timing of binding to chromosome Although human condensins play classical roles in and mutant phenotypes of dysfunction strongly indicated chromosome dynamics during mitosis, their nonmitotic that human condensin I and II have fundamentally dis- functions have been payed more and more attention than tinct functions during mitosis. Diferent nuclear distribu- before. As a novel function of human condensins in cel- tion, localization on chromosomesof human condensin I lular senescence during interphase, much more problems and human condenisn II during cell cycle are shown as remain to be further explored. Tis paper reviewed the Fig. 1. research progress of human condensins involved in dif- In addition to their mitotic functions, human con- ferent types of cellular senescence, mainly oncogene- densins also play important roles in the prestressed induced senescence (OIS) and replicative senescence Fig. 1 Diferent nuclear distribution, localization on chromosomes of human condensin I and condensin II during cell cycle (one chromosome is illustrated as an example) Wang et al. Cell Biosci (2020) 10:147 Page 3 of 7 (RS). Te future perspectives of human condensins in the upregulation of senescence genes upon senescence. cellular senescence are also discussed. Terefore, the roles of human condensin II in cellular senescence may be through compartmental reorganiza- Human condensins involved in cellular senescence tions coupled to gene regulation [37]. Firstly, human condensins are involved in OIS. Initially, Secondly, human condensins are involved in RS. SMC2 human condensin II is found to play a novel role in OIS. and SMC4, core subunits of human condensins, are dem- Overexpression of human condensin II, but not human onstrated to be down-regulated in the serially passaged condensin I, induces cellular senescence and senescence- fbroblast cells by proteomic study and they are sup- associated heterochromatic foci (SAHF) formation and posed to play an important role in RS [41]. Consistently, depletion of human